DESCRIPTION: Carpal Tunnel Syndrome (CTS) is a common clinical problem that has assumed epidemic proportions and is dramatically increasing in the working population. We have developed an in vivo rabbit model for CTS in which coronary angioplasty balloon catheters are placed within the carpal tunnel and inflated to different pressures for varying lengths of time. We have demonstrated a graded response between carpal tunnel pressure and slowing of the median nerve conduction velocity. Also, we have demonstrated changes in histologic nerve preparations stained with hematoxylin-eosin and osmium (axon dropout and presence of edema and fibrosis). These results demonstrate that key clinical/pathoanatomical features of human CTS are replicated in this model system. The goals of the current proposal are: (1) to utilize this model to investigate the cellular mechanisms by which pressure adversely affects the median nerve, (2) to determine a quantifiable relationship between the time history of carpal tunnel pressure and nerve dysfunction with electron microscopy ultrastructure, blood flow, and MRI, and (3) to investigate whether there exists a threshold of pathoanatomical change below which nerve dysfunction is reversible, and whether such a threshold may be assessed non-invasively. Toward these ends, the current proposal focuses on developing and applying new modalities to the animal CT model: electron microscopy; magnetic resonance imaging. laser doppler blood flow measurement. We hypothesize that in the pathomechanics of CTS, there is a significant relationship between pressure, duration of exposure to pressure and various cellular and vascular events that surround CTS. These data will have significant implications for human CTS. In the future, this model may serve to test the modulation of the threshold pressure for developing CTS by various treatments in an effort to prevent CTS. Ultimately, we wish to realize a comprehensive understanding of pathophysiology of CTS, its prevention, when it occurs, and its treatment. We will simulate clinical CTS reversal, as in carpal tunnel release, by deflating balloon catheters in animals in which CTS has already been induced We anticipate that this model system that specifically relates nerve pathoanatomy, dysfunction and pressure exposure. provides the foundation for future study on the efficacy of pharmacologic and other intervention modalities in human clinical trials.